The role of vascular endothelial growth factor and vascular stability in diseases of the ear.

OBJECTIVES/HYPOTHESIS Vascular endothelial growth factor (VEGF) is a critical mediator of vascular permeability and angiogenesis and likely plays an important role in cochlear function and hearing. This review highlights the role of VEGF in hearing loss associated with vestibular schwannomas, otitis media with effusion, and sensorineural hearing loss. STUDY DESIGN PubMed literature review. METHODS A review of the literature was conducted to determine the role of VEGF in diseases affecting hearing. RESULTS Therapeutic efficacy has been demonstrated for the anti-VEGF agent bevacizumab in vestibular schwannomas, with tumor size reduction and hearing improvement in patients with neurofibromatosis type 2. The loss of functional Merlin, the protein product of the nf2 gene, results in a decrease in expression of the anti-angiogenic protein SEMA3F through a Rac-1-dependent mechanism, allowing VEGF to promote angiogenesis. Bevacizumab may therefore restore the angiogenic balance through inhibiting the relative increase in VEGF. Many of the clinical findings of otitis media with effusion can be reproduced by delivery of recombinant VEGF through transtympanic injection or submucosal osmotic pump. VEGF receptor inhibitors have been demonstrated to improve hearing in an animal model of otitis media with effusion. VEGF affects both the inner ear damage and repair processes in sensorineural hearing loss. CONCLUSIONS VEGF has an important role in vestibular schwannomas, otitis media with effusion, and sensorineural hearing loss.